tbuckley/cabot-search huggingface dataset:
Safety of Antipsychotic Polypharmacy Versus Monotherapy in a Nationwide Cohort of 61,889 Patients With Schizophrenia
Authors: Heidi Taipale, Antti Tanskanen, Jari Tiihonen
Journal: American Journal of Psychiatry (2023)

The authors sought to study the safety of antipsychotic polypharmacy compared with monotherapy in specific dosage categories.Patients with schizophrenia (N=61,889; median follow-up, 14.8 years [IQR=7.4-22.0]) were identified from the Finnish nationwide inpatient care register and followed up over the period 1996-2017. Antipsychotic polypharmacy was compared with monotherapy in seven dosage categories (<0.4, 0.4-<0.6, 0.6-<0.9, 0.9-<1.1, 1.1-<1.4, 1.4-<1.6, and ≥1.6 defined daily doses [DDDs] per day) in terms of risk of severe physical morbidity, indicated by nonpsychiatric and cardiovascular hospitalizations (adjusted hazard ratio). Within-individual analysis was used in an effort to eliminate selection bias.The mean age of the cohort was 46.7 years (SD=16.0), and 50.3% (N=31,104) were men. Among patients who had used both monotherapy and polypharmacy, the risk of nonpsychiatric hospitalization was significantly lower during polypharmacy use at all total dosage categories above 1.1 DDDs/day with differences up to -13% than during monotherapy use of the same dosage category (for 1.1-<1.4 DDDs/day, adjusted hazard ratio=0.91, 95% CI=0.87-0.95; for 1.4-<1.6 DDDs/day, adjusted hazard ratio=0.91, 95% CI=0.86-0.96; and for ≥1.6 DDDs/day, adjusted hazard ratio=0.87, 95% CI=0.84-0.89). The risk of cardiovascular hospitalization was significantly lower for polypharmacy at the highest total dosage category (-18%, adjusted hazard ratio=0.82, 95% CI=0.72-0.94). The results from the comparisons between monotherapy and no use and between polypharmacy and no use were in line with the primary comparison of polypharmacy and monotherapy within the same individual. Comparison of any polypharmacy use with any monotherapy use showed no significant difference for nonpsychiatric or cardiovascular hospitalization.The results show that antipsychotic monotherapy is not associated with a lower risk of hospitalization for severe physical health problems when compared with antipsychotic polypharmacy. Treatment guidelines should not encourage use of monotherapy instead of antipsychotic polypharmacy without any existing evidence on the safety issues.
Assessment of Team Dynamics and Operative Efficiency in Hip and Knee Arthroplasty
Authors: Henry C. Cousins, Eli M. Cahan, Joshua T. Steere, William J. Maloney, Stuart B. Goodman, Matthew D. Miller, James I. Huddleston, Derek F. Amanatullah
Journal: JAMA Surgery (2023)

Surgical team communication is a critical component of operative efficiency. The factors underlying optimal communication, including team turnover, role composition, and mutual familiarity, remain underinvestigated in the operating room.
<i>JAMA Surgery</i>—The Year in Review, 2022
Authors: Melina R. Kibbe
Journal: JAMA Surgery (2023)

was a year associated with tremendous accomplishments for JAMA Surgery.First, as evidence of the highquality scientific publications in JAMA Surgery, the impact factor rose from 14.8 to 16.7.This remarkable achievement reflects the hard work of the journal's authors, peer reviewers, and editorial team.The impact factor, along with other important metrics, continues to position JAMA Surgery as the number 1 ranked surgery journal in the world.In 2022, the acceptance rate for all article types was 19%; for Original Investigations, 8%; and for Research Letters, 17%.2][3][4][5][6][7][8][9] The web and social media presence for JAMA Surgery continues to be strong under the leadership of Amalia L. Cochran, MD, the Web and Social Media Editor.More than 4.6 million articles were viewed and downloaded from the journal website in 2022.The journal's electronic table of contents is delivered each week to more than 126 000 individuals.We currently have 47 500 Twitter followers, which represents an 11.6% increase in 2022, and 27 161 Facebook followers, which represents a 0.3% increase in 2022 (Table ).Thus, between the electronic table of contents, visits to the journal website, social media reach, and print distribution, JAMA Surgery reaches more than 130 000 individuals weekly.
Decellularized Liver Nanofibers Enhance and Stabilize the Long‐Term Functions of Primary Human Hepatocytes In Vitro
Authors: Jennifer S. Liu, Liszt Y. C. Madruga, Yang Yuan, Matt J. Kipper, Salman R. Khetani
Journal: Advanced Healthcare Materials (2023)

Abstract Owing to significant differences across species in liver functions, in vitro human liver models are used for screening the metabolism and toxicity of compounds, modeling diseases, and cell‐based therapies. However, the extracellular matrix (ECM) scaffold used for such models often does not mimic either the complex composition or the nanofibrous topography of native liver ECM. Thus, here novel methods are developed to electrospin decellularized porcine liver ECM (PLECM) and collagen I into nano‐ and microfibers (≈200–1000 nm) without synthetic polymer blends. Primary human hepatocytes (PHHs) on nanofibers in monoculture or in coculture with nonparenchymal cells (3T3‐J2 embryonic fibroblasts or primary human liver endothelial cells) display higher albumin secretion, urea synthesis, and cytochrome‐P450 1A2, 2A6, 2C9, and 3A4 enzyme activities than on conventionally adsorbed ECM controls. PHH functions are highest on the collagen/PLECM blended nanofibers (up to 34‐fold higher CYP3A4 activity relative to adsorbed ECM) for nearly 7 weeks in the presence of the fibroblasts. In conclusion, it is shown for the first time that ECM composition and topography synergize to enhance and stabilize PHH functions for several weeks in vitro. The nanofiber platform can prove useful for the above applications and to elucidate cell‐ECM interactions in the human liver.
Erythema and Induration after Mpox (JYNNEOS) Vaccination Revisited
Authors: Sharon E Frey, Johannes B Goll, John H Beigel
Journal: New England Journal of Medicine (2023)

ents of the bivalent vaccine as compared with recipients of the monovalent vaccine.The evaluated events included ischemic stroke (hazard ratio, 0.86; 95% confidence interval [CI], 0.58 to 1.27), hemorrhagic stroke (hazard ratio, 0.86; 95% CI, 0.46 to 1.61), myocardial infarction (hazard ratio, 0.92; 95% CI, 0.62 to 1.36), pulmonary embolism (hazard ratio, 0.83; 95% CI, 0.49 to 1.40), and all four events combined (hazard ratio, 0.87; 95% CI, 0.69 to 1.09) (Table 1).Thus, our results provide reassurance regarding the continued use of this bivalent vaccine.
Organ Transplants From Deceased Donors With Primary Brain Tumors and Risk of Cancer Transmission
Authors: George H. B. Greenhall, Brian A. Rous, Matthew L. Robb, Chloe Brown, Gillian Hardman, Rachel M. Hilton, James M. Neuberger, John H. Dark, Rachel J. Johnson, John L. R. Forsythe, Laurie A. Tomlinson, Chris J. Callaghan, Christopher J. E. Watson
Journal: JAMA Surgery (2023)

Cancer transmission is a known risk for recipients of organ transplants. Many people wait a long time for a suitable transplant; some never receive one. Although patients with brain tumors may donate their organs, opinions vary on the risks involved.To determine the risk of cancer transmission associated with organ transplants from deceased donors with primary brain tumors. Key secondary objectives were to investigate the association that donor brain tumors have with organ usage and posttransplant survival.This was a cohort study in England and Scotland, conducted from January 1, 2000, to December 31, 2016, with follow-up to December 31, 2020. This study used linked data on deceased donors and solid organ transplant recipients with valid national patient identifier numbers from the UK Transplant Registry, the National Cancer Registration and Analysis Service (England), and the Scottish Cancer Registry. For secondary analyses, comparators were matched on factors that may influence the likelihood of organ usage or transplant failure. Statistical analysis of study data took place from October 1, 2021, to May 31, 2022.A history of primary brain tumor in the organ donor, identified from all 3 data sources using disease codes.Transmission of brain tumor from the organ donor into the transplant recipient. Secondary outcomes were organ utilization (ie, transplant of an offered organ) and survival of kidney, liver, heart, and lung transplants and their recipients. Key covariates in donors with brain tumors were tumor grade and treatment history.This study included a total of 282 donors (median [IQR] age, 42 [33-54] years; 154 females [55%]) with primary brain tumors and 887 transplants from them, 778 (88%) of which were analyzed for the primary outcome. There were 262 transplants from donors with high-grade tumors and 494 from donors with prior neurosurgical intervention or radiotherapy. Median (IQR) recipient age was 48 (35-58) years, and 476 (61%) were male. Among 83 posttransplant malignancies (excluding NMSC) that occurred over a median (IQR) of 6 (3-9) years in 79 recipients of transplants from donors with brain tumors, none were of a histological type matching the donor brain tumor. Transplant survival was equivalent to that of matched controls. Kidney, liver, and lung utilization were lower in donors with high-grade brain tumors compared with matched controls.Results of this cohort study suggest that the risk of cancer transmission in transplants from deceased donors with primary brain tumors was lower than previously thought, even in the context of donors that are considered as higher risk. Long-term transplant outcomes are favorable. These results suggest that it may be possible to safely expand organ usage from this donor group.
Comprehensive Framework of Firearm Violence Survivor Care
Authors: Sydney C. Timmer-Murillo, Mary E. Schroeder, Colleen Trevino, Timothy J. Geier, Andrew T. Schramm, Amber M. Brandolino, Stephen Hargarten, Daniel Holena, Marc de Moya, David Milia, Terri A. deRoon-Cassini
Journal: JAMA Surgery (2023)

Firearm violence is a public health crisis placing significant burden on individuals, communities, and health care systems. After firearm injury, there is increased risk of poor health, disability, and psychopathology. The newest 2022 guidelines from the American College of Surgeons Committee on Trauma require that all trauma centers screen for risk of psychopathology and provide referral to intervention. Yet, implementing these guidelines in ways that are responsive to the unique needs of communities and specific patient populations, such as after firearm violence, is challenging.The current review highlights important considerations and presents a model for trauma centers to provide comprehensive care to survivors of firearm injury. This model highlights the need to enhance standard practice to provide patient-centered, trauma-informed care, as well as integrate inpatient and outpatient psychological services to address psychosocial needs. Further, incorporation of violence prevention programming better addresses firearm injury as a public health concern.Using research to guide a framework for trauma centers in comprehensive care after firearm violence, we can prevent complications to physical and psychological recovery for this population. Health systems must acknowledge the socioecological context of firearm violence and provide more comprehensive care in the hospital and after discharge, to improve long-term recovery and serve as a means of tertiary prevention of firearm violence.
Regulation of beta‐amyloid for the treatment of Alzheimer's disease: Research progress of therapeutic strategies and bioactive compounds
Authors: Weimin Qiu, Hui Liu, Yijun Liu, Xin Lu, Lei Wang, Yanyu Hu, Feng Feng, Qi Li, Haopeng Sun
Journal: Medicinal Research Reviews (2023)

Alzheimer's disease (AD) is a progressive neurodegenerative disease that is difficult to treat. Extracellular amyloid is the principal pathological criterion for the diagnosis of AD. Amyloid β (Aβ) interacts with various receptor molecules on the plasma membrane and mediates a series of signaling pathways that play a vital role in the occurrence and development of AD. Research on receptors that interact with Aβ is currently ongoing. Overall, there are no effective medications to treat AD. In this review, we first discuss the importance of Aβ in the pathogenesis of AD, then summarize the latest progress of Aβ-related targets and compounds. Finally, we put forward the challenges and opportunities in the development of effective AD therapies.
Genital Pseudotumor as a Manifestation of Mpox Virus Infection
Authors: François-Xavier Blanchet, Mayda Rahi, Marie Merlant, Mathilde Gare, Florence Brunet-Possenti, Vincent Descamps, Fabrice Bouscarat
Journal: JAMA Dermatology (2023)

This case report describes a 37-year-old man with a 1-week history of a genital nodule that rapidly ulcerated and with concomitant fever 2 days after anal intercourse.
Case 9-2023: A 20-Year-Old Man with Shortness of Breath and Proteinuria
Authors: Shaun F. Fitzgerald, Teresa Victoria, Weizhen Tan, Cynthia K. Harris
Journal: New England Journal of Medicine (2023)

A 20-year-old man was admitted with hemoptysis and hypoxemia. CT of the chest revealed pulmonary emboli; urinalysis showed proteinuria and hematuria. Diagnostic tests were performed.
Correspondence on 'H3.3K27M mutation is not a suitable target for immunotherapy in HLA-A2+ patients with diffuse midline glioma' by Immisch<i>et al</i>
Authors: Zinal S Chheda, Sabine Mueller, Bindu Hegde, Akane Yamamichi, Lisa H Butterfield, Hideho Okada
Journal: Journal for ImmunoTherapy of Cancer (2023)

We read with interest the article entitled, 'H3.3K27M mutation is not a suitable target for immunotherapy in HLA-A2+ patients with diffuse midline glioma' (DMG).[1][1] In this report, the investigators isolated an H3.3K27M-specific T cell receptor (TCR) from transgenic mice expressing a diverse
ROS Induction Targets Persister Cancer Cells with Low Metabolic Activity in NRAS-Mutated Melanoma
Authors: Ossia M. Eichhoff, Corinne I. Stoffel, Jan Käsler, Luzia Briker, Patrick Turko, Gergely Karsai, Nina Zila, Verena Paulitschke, Phil F. Cheng, Alexander Leitner, Andrea Bileck, Nicola Zamboni, Anja Irmisch, Zsolt Balazs, Aizhan Tastanova, Susana Pascoal, Pål Johansen, Rebekka Wegmann, Julien Mena, Alaa Othman, Vasanthi S. Viswanathan, Judith Wenzina, Andrea Aloia, Annalisa Saltari, Andreas Dzung, Michael Krauthammer, Stuart L. Schreiber, Thorsten Hornemann, Martin Distel, Berend Snijder, Reinhard Dummer, Mitchell P. Levesque
Journal: Cancer Research (2023)

Abstract Clinical management of melanomas with NRAS mutations is challenging. Targeting MAPK signaling is only beneficial to a small subset of patients due to resistance that arises through genetic, transcriptional, and metabolic adaptation. Identification of targetable vulnerabilities in NRAS-mutated melanoma could help improve patient treatment. Here, we used multiomics analyses to reveal that NRAS-mutated melanoma cells adopt a mesenchymal phenotype with a quiescent metabolic program to resist cellular stress induced by MEK inhibition. The metabolic alterations elevated baseline reactive oxygen species (ROS) levels, leading these cells to become highly sensitive to ROS induction. In vivo xenograft experiments and single-cell RNA sequencing demonstrated that intratumor heterogeneity necessitates the combination of a ROS inducer and a MEK inhibitor to inhibit both tumor growth and metastasis. Ex vivo pharmacoscopy of 62 human metastatic melanomas confirmed that MEK inhibitor–resistant tumors significantly benefited from the combination therapy. Finally, oxidative stress response and translational suppression corresponded with ROS-inducer sensitivity in 486 cancer cell lines, independent of cancer type. These findings link transcriptional plasticity to a metabolic phenotype that can be inhibited by ROS inducers in melanoma and other cancers. Significance: Metabolic reprogramming in drug-resistant NRAS-mutated melanoma cells confers sensitivity to ROS induction, which suppresses tumor growth and metastasis in combination with MAPK pathway inhibitors.
Risk of developing a second primary melanoma after a first primary melanoma in a population-based Australian cohort
Authors: Yuan Ni, Caroline G Watts, Richard A Scolyer, Christine Madronio, Bruce K Armstrong, Rachael L Morton, Scott W Menzies, Graham J Mann, John F Thompson, Serigne N Lo, Anne E Cust
Journal: British Journal of Dermatology (2023)

This cross-sectional survey identified risk factors for developing a second primary melanoma. Patients with melanoma who had characteristics such as male sex, older age, high naevus count, or melanoma on the trunk or upper limbs had a substantially higher risk of subsequent melanoma and should therefore be more intensively monitored.
<i>JAMA Dermatology</i>—The Year in Review, 2022
Authors: Kanade Shinkai
Journal: JAMA Dermatology (2023)

JAMA Dermatology continued to thrive in 2022.The editorial leadership team carefully evaluated 2745 article submissions during the past year (Table ).A total of 1300 of 2745 submissions (47%) were research articles, which was similar to the previous year.Acceptance rates also remained stable, with 10% of submissions overall and 11% of research articles accepted for publication.With an ongoing commitment to publishing excellence and process improvement, the journal continued to maintain its goal of reducing the time to publication, keeping the median days of acceptance to publication to 61 days while offering timely editorial decisions, including maintaining its median receipt-to-rejection time of 4 days and me-dian receipt to first decision with peer review of 42 days.The editorial leadership team continued to strive to find ways to improve authors' experience to ensure authors the fastest and best publication of their work.As predicted in last year's review, many of the top dermatology journals achieved substantial increases in impact factors, which was likely a reflection of COVID-19 skin-related publications, and in line with trends seen across the medical literature.JAMA Dermatology's impact factor increased from 10.3 to 11.8.The journal broadened its digital reach, with more than 5.2 million full-text views and downloads in the past year (an approximately 20% increase), and expanded its connections to more than 68 000 followers on the social media channels Twitter, Facebook, and Instagram, a 15% increase compared with the previous year.The highest-viewed papers included randomized clinical trials for psoriasis 1 and atopic dermatitis. 2 The article by Simpson et al 2 presented longterm (52 weeks) efficacy and safety data for upadacitinib treatment in patients with atopic dermatitis.It comes as no surprise that the third of the top 3 articles by views and downloads, as well as one of the top 3 articles by
Duplication and Losses of Opsin Genes in Lophotrochozoan Evolution
Authors: Giacinto De Vivo, Fabio Crocetta, Miriam Ferretti, Roberto Feuda, Salvatore D’Aniello
Journal: Molecular Biology and Evolution (2023)

Opsins are G-coupled receptors playing a key role in metazoan visual processes. While many studies enriched our understanding of opsin diversity in several animal clades, the opsin evolution in Lophotrochozoa, one of the major metazoan groups, remains poorly understood. Using recently developed phylogenetic approaches, we investigated the opsin evolution in 74 lophotrochozoan genomes. We found that the common ancestor of Lophotrochozoa possessed at least seven opsin paralog groups that underwent divergent evolutionary history in the different phyla. Furthermore, we showed for the first time opsin-related molecules in Bilateria that we named pseudopsins, which may prove critical in uncovering opsin evolution.
Trends in the Use of Oral Anticoagulants for Adults With Venous Thromboembolism in the US, 2010-2020
Authors: Geetha S. Iyer, Helen Tesfaye, Nazleen F. Khan, Heidi Zakoul, Katsiaryna Bykov
Journal: JAMA Network Open (2023)

The introduction of direct oral anticoagulants (DOACs) has transformed the treatment of venous thromboembolism (VTE). Large health care databases offer valuable insight into how oral anticoagulants (OACs) are used in clinical practice and may aid in understanding reasons for changes in therapy.To evaluate prescribing patterns of OACs for patients with VTE and identify clinical events that precede treatment changes.This retrospective cohort study used data from a public (Medicare fee-for-service) and a commercial (IBM MarketScan) health insurance database on 298 609 patients initiating OACs within 90 days of index VTE hospitalization from January 1, 2009, to December 31, 2020. Statistical analysis was conducted from April to August 2022.Warfarin and the DOACs rivaroxaban, apixaban, dabigatran, and edoxaban.Characteristics of patients initiating different OACs, along with trends over time of patients initiating OACs, were compared. Time receiving continuous anticoagulant therapy, patterns of anticoagulant discontinuation (treatment gap of ≥30 days), and treatment switches were assessed. Clinical events in the 30 days preceding treatment modifications were identified.A total of 203 378 individuals with Medicare (mean [SD] age, 76.9 [7.6] years; 122 554 women [60.3%]) and 95 231 with commercial insurance (mean [SD] age, 57.6 [15.8] years; 47 139 women [49.5%]) were included (N = 298 609). Warfarin was the most frequent OAC prescribed (163 044 [54.6%]), followed by rivaroxaban (66 882 [22.3%]) and apixaban (65 997 [22.1%]). The proportion of patients initiating DOACs increased from 0% in 2010 to 86.8% (22 420 of 25 817) in 2019 for patients with Medicare and 92.1% (4012 of 4357) in 2020 for commercially insured patients. Patients with chronic kidney disease were more likely to initiate warfarin (35 561 [11.9%]) or apixaban (16 294 [5.5%]) than rivaroxaban (10 136 [3.4%]), and those with a history of bleeding were more likely to initiate apixaban (5424 [1.8%]) than rivaroxaban (3007 [1.0%]). Overall, patients received persistent OAC treatment for approximately 6 months (Medicare: median, 175 days [IQR, 76-327 days]; commercial insurance: median, 168 days [IQR, 83-279 days]). A total of 33 011 patients (11.1%) switched anticoagulant therapy within a year. Switching to another anticoagulant was preceded most frequently by codes for a VTE diagnostic procedure (27.2% of all switchers [8983 of 33 011]).This cohort study using data from 2 US health insurance databases suggests that most patients with VTE continued oral anticoagulant treatment for approximately 6 months. Clinical reasons for modifying anticoagulant therapy were identified in one-third of patients. Identifying reasons for treatment modification is crucial for generating valid evidence on drug safety and effectiveness.
Investigator Global Assessment for impetiginization in atopic dermatitis: development and initial reliability testing
Authors: Aviël Ragamin, Ron A Tupker, Marlies de Graaf, Thomas Rustemeyer, Suzanne G M A Pasmans, Renske Schappin, Marie L A Schuttelaar
Journal: British Journal of Dermatology (2023)

Secondary infections with Staphylococcus aureus (i.e. impetiginization) are common in patients with atopic dermatitis (AD). However, a scale to assess the severity of impetiginization is lacking. This study aimed to develop and investigate an Investigator Global Assessment (IGA) for impetiginization in AD (‘IGA impetiginization’). Consensus was achieved for a 3-point IGA scale containing a description of clinical signs and extent of the affected area. Substantial inter-rater reliability [intraclass correlation coefficient (ICC) 0.68], good intra-rater reliability (ICC 0.81) and good overall agreement (81%) were found. The IGA impetiginization is a simple scale for the assessment of impetiginization in AD that could be used in clinical practice and research.